Tuesday, January 5, 2016

Where does Silberman get his info on autism genetic research?

In the continued saga of Steve Silberman strangeness, I just happened to be reading a piece written a few months ago by this person who is now the most prominent popular writer on autism related matters.  The piece has (at least to me) the offensive title Autism is a valuable part of humanity's genetic legacy. The phrase that stands out most prominently to me in the article is this:

 In recent years, researchers have determined that most cases of autism are not rooted in rare de novo mutations but in very old genes that are shared widely in the general population while being concentrated more in certain families than others. 

Since Silberman neglected to cite any source for this, I'm curious where he got this information since it completely contradicts everything that I've read about autism genetic research that's taken place in the last eight years or so.


Jonathan Sebat for instance has published research showing a significant association between autism and de novo mutations.  Dr. Sebat states that he expects that the actual cases of de novo mutations is in reality substantially higher than what he found since the techniques for identifying these genetic abnormalities are still not advanced enough to find spontaneous mutations on the genome that might be even smaller than those already identified.

A study done in Israel several years ago showed that children of fathers over the age of forty were nearly six times as likely to have an autism spectrum disorder than the offspring of younger fathers.  It was considered probable that this was the result of de novo mutations in the sperm of the older dads. 

A very recent study done at Cold Harbor Springs lab has suggested that probably half of all cases of autism are caused by rare de novo mutations on genes that have a particular vulnerability and that these are not old genes as Silberman claims, but are expunged rapidly from the population since autistic people rarely have children.  Previous research done by this group showed that some of these de novo mutations were carried by the mothers who had a protective effect against autism but their children (usually boys) inherited them in an autosomal dominant fashion.

This is just a small sampling of articles that suggest rare de novo mutations not found in the general population are a significant factor in autism spectrum disorders.   

The Slate article was apparently excerpted from the Neurotribes book.  It's been a while since I've read neurotribes and I can't recall if Silberman wrote this in the book or if he gave any references to any actual genetic studies that support his statement.   Since there's been so much science that contradicts what he says, I'm wondering if this research exists, could Silberman or anyone else cite any references since I can't seem to find any on the internet.  Maybe there's something out there, but it would seem that Silberman has made statements on the genetics of autism that have no factual basis as was the case with his statements on Kanner's work.  Even if there were such research, Silberman would have to explain why he said what he said in light of  recent research that has found that a significant number of autism cases are the result of de novo mutations.  

7 comments:

Roger Kulp said...

I do not think most advocates of neurodiversity know squat about recent autism research.Yes there are de novo mutations,just as there are with any disease.Ask me I know.I have de novo mutations of one of the rarest neuroimmune diseases in the world.Unlike pretty much everybody in the neurodiversity movement,I have been digging deeply into autism research since 2009.And all I can say is Silberman is full of it,and has no idea what he is talking about.

Autism is a complicated disorder,involving many different genes and systems.Inherited,but not purely genetic in the traditional sense.Autism,we are finding,is due,in part to the sum of many little mutations,called single neucleotide polymorphisms or SNPs.

Autism can also be largely immune,but not entirely.Immune disorders can go hand in hand with these SNPs.There is PANDAS and PANS of course,but there are also any number of immune conditions passed from mother to baby in the womb that can cause or contribute to autism.This includes the folate receptor autoantibodies I have been found to have,that cause cerebral folate deficiency.

Then there are all those inborn metabolic disorders.

This is all stuff that has been recently discovered in the last ten years or less.Much of which would explain the regression after vaccines.

I don't consider 50 some people come to some stupid "Autreat" a huge turnout.

jonathan said...

Roger: Autism is probably not just one distinct disorder, but the result of many different etiologies which produces a similar but not identical phenotype in a number of people that's been called the same name. I don't think SNP's are the only cause of autism, but there are also copy number variants which include deletions of certain genes or parts of certain genes. Based on research done in the last several years by many different groups, there's little doubt that a lot of them are caused by de novo mutations, though I suppose not all of them. Maybe there are others that are caused by groups of old genes that stayed within the population, but I'd be interested in some documentation of that. You're probably correct about most ND's not knowing much about recent autism research, but perhaps there is something out there I missed, but i'm still waiting for silberman or anyone else to inform me in the comments section.

Frank Kelly said...

There are two camps - the common variation camp and the de novo camp and they are fighting it out

Silberman only quoted one camp - here is a recent paper

Gaugler et al (2014) Most genetic risk for autism resides with common variation. Nat Genet. 2014 August ; 46(8)
Abstract: Narrow-sense heritability is ~54% and most traces to common variation. Rare de novo mutations contribute substantially to individual’s liability still their contribution to variance in liability is 2.6%


compare to

Geschwind and State (2015) Gene hunting in autism spectrum disorder: on the path to precision medicine

From an evolutionary standpoint, such common variation would be predicted to be under strong selection pressure making it unlikely that common variation would have strong or even moderate negative effects on early survival or reproductive fitness


Likely there's a bit of both - not to mention epigenetic factors and environmental ones too.

spinoff said...

Yes Frank
And there are some curious things too:
The much higher prevalence in grand premtures particularly associated with retinopathy. Prematurity is common in twins, are they not more vulnerable because of the twinship itself? How many afected had a twin that aborted spontaneously? I have known some of both. What about those born of foreigm mothers? Or those born of mothers who were grossly abused as girls? I understand that the prevalence is higher in them

I have seem quite a few parents with characteristics of autism, failures in social reciprocity, excessive and even brilliant attention to details and mechanisms, etc. I do wonder if there is a sort of replication problem similar to Fragile X. The number of copies of a fragmente of ADN, gen or not, grow from generation to generatio till there is Kanners autism.

Anonymous said...

" I have seem quite a few parents with characteristics of autism, failures in social reciprocity, excessive and even brilliant attention to details and mechanisms, etc. "

Those are behaviors. Behaviors can be taught. http://www.wsj.com/articles/SB10001424052748704111504576059713528698754 is about a mother actively teaching her children to fail at social reciprocity, pay excessive and even brilliant attention to the details and mechanisms of her favorite musical instruments, etc.

spinoff said...

Of course you can teach behaviours, particularly if you are a chinese mother. And if you use slaps and electroshocks, as Lovaas did, you can teach behaviours even to autistic people, although there is polemic about the methodology, and the generalization and duration of effects.

But that was not my point. Or are you saying that autism is a learnt disorder?

Learning is favoured by various "orienting stimuli" and is that learning which precedes language, social interaction, contexts and synthesis, that some people on the spectrum find difficult. For this we have to suspect that there are organic defficiencies, which difficult that learning and that is what research indicates.

Better a few images over a missing sock:
talking twin babies - part 2 - official video - youtube
That is the learning for which you do not neeed chinese mothers if you are neurotypical.

Anonymous said...

I'm not saying that autism is a learnt disorder.

I'm saying failures in social reciprocity, excessive and even brilliant attention to details and mechanisms, etc. are not *only* symptoms of autism. They are also behaviors taught by some non-autistic people to some other non-autistic people.